Levosimendan Versus Placebo Before Tricuspid Valve Surgery in Patients With Right Ventricular Dysfunction

Phase 3

Recruiting

Conditions: Patients Referred for an Isolated or a Combined Surgical Correction of Functional Moderate to Severe Tricuspid

Brief Summary: A Prospective, multicenter, randomized (two arms, parallel groups); double-blind, placebo-controlled in order to assess the ability of preoperative levosimendan to prevent post-operative low cardiac output in high-risk patients referred to cardiac surgery for correcting functional tricuspid regurgitation. The primary end point is a composite element that includes peri-operative mortality and low cardiac output syndrome at day-90: 1) catecholamine infusion persisting beyond 48 hours after cardiac surgery, 2) the need for circulatory mechanical assist devices in the postoperative period, 3) or the need for renal replacement therapy at any time during intensive care unit stay. If a patient had at least 1 of these criteria, he or she was considered as meeting the primary end point.The secondary end points were 1) each component of the primary end point, and 2) the study drug safety defined as refractory hypotension.

Detailed Description: Patients referred for an isolated or a combined surgical correction of functional moderate to severe tricuspid are randomized in 2 arms, the levosimendan group or to the placebo group.

In the experimental group, levosimendan is administered as a continuous infusion over a 24-hour period at the rate of 0.2μg/kg/min, with no bolus administration. The infusion will begin 24H to 48H before anesthetic induction.

In the comparator group, Placebo (isotonic sodium) administered as a continuous infusion over a 24-hour period at the rate of 0.2μg/kg/min, with no bolus administration. The infusion will begin \<48H before anesthetic induction

Recruitment & Eligibility

Inclusion Criteria

Patients referred for an isolated or a combined surgical correction of functional moderate to severe tricuspid regurgitation [effective regurgitant orifice (ERO)>20mm², or systolic hepatic vein flow blunting or reversal]
Written signed informed consent
Affiliation to the French health care system (Sécurité Sociale)

Exclusion Criteria

Age < 18 years
Severe organic renal dysfunction defined by creatinine clearance <30mL/min
Recent endocarditis (<3 months)
Recent myocardial infarction (<3 months)
Tricuspid valve perforation or prolapse
Cardiogenic shock requiring dobutamine support or cardiac assistance
Severe liver injury (CHILD C)
Left ventricular obstruction
Allergy to levosimedan
Current participation in other investigational drug or device studies or being in the exclusion period at the end of a previous study involving human participants, if applicable
Pregnant or breastfeeding women
Females of childbearing potential without effective method of birth control
Patient on AME (state medical aid) unless exemption from affiliation
Hypotension with SBP<90mmHg
Severe tachycardia
History of torsade de pointe

Arm && Interventions

Group	Intervention	Description
PLACEBO	PLACEBO	Placebo (isotonic sodium) administered as a continuous infusion over a 24-hour period at the rate of 0.2μg/kg/min, with no bolus administration. The infusion will begin \<48H before anesthetic induction.
LEVOSIMEDAN	Levosimendan	Levosimendan administered as a continuous infusion over a 24-hour period at the rate of 0.2μg/kg/min, with no bolus administration. The infusion will begin 24H to 48H before anesthetic induction.

Primary Outcome Measures

Name	Time	Method
Evaluate the effects of CTAC on ventilation/perfusion ratios during a moderate to severe ARDS	day 90	The primary end point is a composite element that includes peri-operative mortality and low cardiac output syndrome at day-90: 1) catecholamine infusion persisting beyond 48 hours after cardiac surgery, 2) the need for circulatory mechanical assist devices in the postoperative period, 3) or the need for renal replacement therapy at any time during intensive care unit stay. If a patient had at least 1 of these criteria, he or she was considered as meeting the primary end point.

Secondary Outcome Measures

Name	Time	Method
incidence of Refractory Hypotension (Drug safety)	day 90	the study drug safety is defined as a refractory hypotension.
Number of catecholamine infusion	during 90 days	persistence of infusion beyond 48 hours after cardiac surgery
Number of circulatory mechanical assist devices	during 90 days	the need of circulatory mechanical assist devices in the postoperative period
Number of renal replacement therapy	during 90 days	Need for renal replacement therapy at any time during intensive care unit stay

Locations (1): Assistance Publique Hôpitaux de Paris-Hôpital Henri Mondor
🇫🇷
Créteil, France